AUTHOR=Sasaki Toru , Suzuki Shinji , Ono Masanori , Yamamoto Akiko , Bingo Masato , Yamanaka Gaku , Kuroda Masahiko , Inagaki Natsuko , Nishi Hirotaka 

TITLE=Case report: Rare heterozygous variant in the NR5A1 gene causing 46,XY complete gonadal dysgenesis with a non-communicating rudimentary uterus

JOURNAL=Frontiers in Medicine

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1441990

DOI=10.3389/fmed.2024.1441990

ISSN=2296-858X

ABSTRACT=<p>The nuclear receptor subfamily 5 group A member 1 (<italic>NR5A1</italic>) gene encodes NR5A1, also known as steroidogenic factor 1, a crucial transcriptional factor regulating adrenal and gonadal development and function. Although pathogenic variants in <italic>NR5A1</italic> are known to cause a spectrum of disorders of sex development (DSD), individuals with 46,XY DSD with fully female internal and external genitalia are relatively rare. Herein, we present the case of a patient with 46,XY complete gonadal dysgenesis (CGD) who had a non-communicating rudimentary uterus due to a c.132_134del (p.Asn44del) heterozygous in-frame-deletion in <italic>NR5A1</italic> that was diagnosed while treating a pelvic mass in which gynecological malignancy could not be disregarded. Unlike two previous cases with the p.Asn44del variant, this case presented with CGD, a severe DSD phenotype, and we found that the oligogenic inheritance of DSD-causative genes such as <italic>SRY</italic>, <italic>DHX37</italic>, <italic>SLC26A8</italic>, and <italic>CFTR</italic> may have affected the severity of the clinical phenotype.</p>